基于脑功能成像和5-HT信号系统研究抑肝扶脾汤治疗IBS内脏高敏感的中枢机制

Irritable bowel syndrome (IBS) is one of the most common functional bowel diorders. Visceral hypersensitivity and abnormality of cerebrocentric algesthesia domain may be responsible for the IBS's two important pathogenesises. In Traditional Chinese Medicine (TCM), liver-spleen disharmony is widely used to explain the role of brain-gut axis in the pathogenesises of IBS. Despite many studies have shown that the efficacy of Chinese herbal medicine on IBS is closely related to the regulation of 5-hydroxytryptamine (5-HT), the action mechanism remains unclear. On the basis of previous research, the group puts forward the following hypothesis: abnormality of cerebrocentric algesthesia domain exists along with visceral hypersensitivity, and its material basis is related to 5-HT in the brain. The efficacy of yiganfupi decoction in relieving IBS visceral hypersentivity is associated with the adjustment for abnormality of cerebrocentric algesthesia domain and 5-HT signaling system. In this research, a model of visceral hypersentivity in rats will be duplicated. Functional magnetic resonance imaging (fMRI) will be used to analyze the relativity of cerebrocentric algesthesia domain and visceral hypersensitivity, and Western blotting will be adopted to analyze the protein expression of SERT, 5-HT2aR, 5-HT7R and SP in the hypothalamus, dorsal root ganglion of spinal cord and colon tissue. Thus, the cerebrocentric mechanisms of yiganfupi decoction on treating IBS visceral hypersensitivity rats will be further demonstrated from the way of brain, spinal cord and bowel. Overall, this research will not only help to clarify the therapeutic mechanism of yiganfupi decoction, but also be beneficial to find potential therapeutic targets. Accordingly, new ideas of the precaution and treatment on IBS may be put forward in TCM.

肠易激综合征（IBS）是最常见的功能性肠病之一，内脏敏感性增高与脑中枢痛觉功能区异常是两种可能的重要发病机制。中医学多从肝脾失调探讨脑肠轴在IBS发病中的作用。大量研究表明中药治疗IBS与调节5-HT密切相关，但具体机制尚不明确。我们在前期研究基础上提出科学假设：内脏高敏感在脑中枢存在痛觉功能区异常，其物质基础与中枢5-HT有关，中药有效方抑肝扶脾汤能通过调节5-HT信号系统和改善脑中枢痛觉功能区异常而降低IBS内脏高敏感。本研究拟通过复制IBS内脏高敏感大鼠模型，采用fMRI分析大鼠脑部痛觉功能区域与内脏高敏感的相关性，Western blot检测下丘脑、脊髓背根神经节和结肠组织SERT、5-HT2aR、5-HT7R、SP蛋白表达，从脑-脊髓-肠途径揭示抑肝扶脾汤治疗IBS内脏高敏感的中枢机制。本研究将阐明抑肝扶脾汤的作用机理，并有助于发现潜在的干预靶点，为中医药防治IBS提供新的思路。

肠易激综合征（IBS）是最常见的功能性肠病之一，内脏敏感性增高与脑中枢痛觉功能区异常是两种可能的重要发病机制。中医学多从肝脾失调探讨脑肠轴在IBS发病中的作用。大量研究表明中药治疗IBS与调节5-HT密切相关，但具体机制尚不明确。我们在前期研究基础上提出科学假设：内脏高敏感在脑中枢存在痛觉功能区异常，其物质基础与中枢5-HT有关，中药有效方抑肝扶脾汤能通过调节5-HT信号系统和改善脑中枢痛觉功能区异常而降低IBS内脏高敏感。本研究在“天癸至神理论”指导下提出了“至神失调致肝脾不和”是本病的关键病机，较之单纯的“肝脾不和”认识更能切中病要，而且“至神-肝脾”与西医学的脑肠互动发病学说有着密切关联。通过本项目研究，验证了“调至神、和肝脾”代表方抑肝扶脾汤能有效治疗IBS，并进一步从脑功能成像和5-HT信号系统研究抑肝扶脾汤的中枢机制，揭示了抑肝扶脾汤降低内脏高敏感的作用可能与改善脑部痛觉功能区异常、调节脑肠轴及5-HT信号系统有关。研究结果有助于阐明IBS病理生理机制及发现潜在的干预靶点，能为中医药防治IBS提供新的思路和科学依据，并为后续开展“调至神、和肝脾”临床应用研究打下基础。